Many a playwright writes something new that takes him to the next level. Neil Simon had “Lost in Yonkers”; for Christopher Durang, it’s “Vanya and Sonia and Masha and Spike.”

The 2012 comedy is a far cry from previous laugh-driven works like “Beyond Therapy,” “Baby With the Bathwater” and “Titanic.” So adept is its mixture of humor and heart that some might even call it Durang’s magnum opus.

At South Coast Rep, director Bart DeLorenzo and a superb cast of six nail the subtleties of this comedic refraction of Chekhov with effortless style and verve.

True to Chekhov, the opening scene depicts the minute details in the everyday lives of Vanya (Tim Bagley) and Sonia (Jenna Cole).

Durang introduces two flies into the ointment of the siblings’ lives: Spike takes a fancy to Nina (Lorena Martinez), an aspiring ingenue whose uncle and aunt are Vanya and Sonia’s neighbors, stoking romantic jealousy within Masha.

And Masha, an actress whose career has begun to peter out, announces she’s planning to put the family home on the market, generating considerable anxiety for her older sibs.

Elements of the show-biz world are prominent throughout Durang’s script. The siblings’ parents loved the great Russian playwrights (hence their kids’ exotic names) and dabbled in community theater. Masha is known both through stage and screen, while Spike has been trying to break into reality series’ on cable TV.

Along the same lines, Nina idolizes Masha and looks to her for career advice, and Vanya has written a play he says is a direct extension of a play written by Constantine in Chekhov’s “The Cherry Orchard.” Since that fictional play is only referred to, Vanya has written what he imagines it would have been, then taps Nina and Sonia to help him present a staged reading.

It’s all artfully Chekhovian, and so much more subtle and layered than Durang’s earlier work. Its story and characters are enjoyably, engagingly loopy, but in addition to the huge laughs, the play also has heart.

DeLorenzo achieves a delicious synergy among his six actors. Bagley’s Vanya is, as scripted, lightly effeminate but not excessively so. More precise and orderly than Sonia, he’s the family conciliator, mediating between the constantly sparring Sonia and Masha. His gently artistic temperament emerges through the abstract play he has written.

Spike’s thoughtless rudeness during the staged reading of Vanya’s new play unleashes a tirade from Vanya that catalogs the loss and destruction of cherished cultural and societal norms of mid-20th-century America, from Ed Sullivan and Davy Crockett to letter-writing and the rotary phone. A focal scene of “Vanya and Sonia” and, at SCR, the monologue is a highlight sure to elicit bursts of applause for expressing unspoken frustrations shared by many.

Given to sad introspection, self-pitying Sonia finds a sense of self-confidence while playing the “role” of Maggie Smith at a costume party – perhaps for the first time ever. Via Cole’s portrayal, the character goes from frumpy duckling to whimsically haughty grand dame. For much of act two, Cole does a killer Maggie Smith impersonation, including during a lovely act two solo scene on the phone.

Very much the narcissistic Hollywood and New York diva, Gray’s Masha genuinely believes she’s a world-class thespian (not even close) and a bright star around whom others orbit. Constantly tooting her own horn, she has no qualms about using others – notably her older siblings and their eccentric cleaning lady Cassandra (Svetlana Efremova).

Yet along with showing Masha’s more laughable traits, Gray also adeptly gives us wonderful peeks beneath the character’s polished exterior, including a raft of wistful insecurities.

Scene-stealing Brooks’ Spike is a tall, slim, free-spirited, musclebound exhibitionist with the hyperactive nature of a 10-year-old boy – very much more a Chippendale boy than a serious actor. Brooks not only folds in a disarming sweetness and endearingly funny idiosyncrasies; he also skillfully shows how Spike’s goofily good-hearted persona is a façade.

Martinez’s Nina is aptly sweet, modest, unassuming and self-effacing, her youthful optimism appealing not only to Vanya but to us as well.

Cassandra functions as a counterbalance to Nina, and speaking with a heavily Slavic accent, Efremova shows finely honed comic timing in the role. A more typically loopy Durang figure, the character issues a steady stream of comically clichéd warnings, all dire and all tied directly to the lives of Vanya, Sonia and Masha.

Keith Mitchell’s scenic design of the family’s rural farmhouse is light, open and airy – not so much cheery as it is a realistic reflection of Vanya and Sonia’s eccentric natures. It’s visually complemented by Raquel Barreto’s costumes.

PREVIEW: Director Bart DeLorenzo indulges his love for Chekhov and Durang in the latest offering at South Coast Rep.

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